Piperidine, 4-(4-iodo-1H-pyrazol-1-yl)-

Endpoint summary

Description of key information

A acute oral study with Wistar rats (Beerens- Heijnen., 2010)  is available which is key study. The oral LD50 value of the test substance was established to be within the range of 50-300 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 200 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 3 September to 12 October 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Wistar strain, Crl:WI (Han) (outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Approx. 8-10 weeks old
- Weight at study initiation: Bodyweight variation was within +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
- Housing: Housed in a controlled environment
- Diet (e.g. ad libitum): Free access to pelleted rodent diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0ºC (actual range: 19.6 - 21.6ºC)
- Humidity (%): A relative humidity of 40-70% (actual range: 42 - 75%)
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN-LIFE DATES: From: 3 September 2010 To: 12 October 2010

Route of administration:

oral: gavage

Vehicle:

other: 1% Aqueous carboxymethyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Lot/batch no. (if required):
- Purity: 1% w/v

Doses:

Dose level (volume) 2000 mg/kg (10 mL/kg) body weight
300 mg/kg (10 mL/kg) body weight
50 mg/kg (10 mL/kg) body weight

No. of animals per sex per dose:

2000 mg/kg body weight 3 females
300 mg/kg body weight 3 females
50 mg/kg body weight 3 females
50 mg/kg body weight 3 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability Twice daily. Body weights Days 1 (pre-administration), 8 and 15. Clinical signs At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day15.
- Necropsy of survivors performed: yes. The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Sex:

female

Dose descriptor:

LD50

Effect level:

50 - 300 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: LD50 cut off was considered to be 200 mg/kg

Mortality:

No death at 50 mg/kg. For concentration 300 and 2000 mg/kg, all animals died two hours after dosing.

Clinical signs:

other: No clinical signs were noted in the animals at 2000 and 300 mg/kg, which all died two hours after dosing.. All animals at 50 mg/kg showed hunched posture on Day 1 and/or 2. In addition three animals showed piloerection and lethargy on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of the test substance in Wistar rats was established to be within the range of 50-300 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 200 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Quality of whole database:

1 (reliable without restriction)

Additional information

A acute oral study with Wistar rats (Beerens- Heijnen., 2010) was conducted accroding to OECD 423. The oral LD50 value of the test substance was established to be within the range of 50-300 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 200 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
Study run to a method comparable with current guidelines and to GLP

Justification for classification or non-classification

Based on the avaliable data, the substance was classfied as Toxicity Category III accroding to Regulation (EC) No. 1272/2008 Table 3.1.1.